1-Alkyl,1-phenyl-butenes

ABSTRACT

The compounds are 4-phenyl-4-lower alkyl-substituted-3-buten-2-ones, and -2-halo-1,3-butadienes, e.g., 2-(p-biphenylyl)-2-penten-4-one, and are useful as pharmaceuticals.

This is a continuation of application Ser. No. 656,785 filed Feb. 10,1979, now abandoned, which in turn is a continuation-in-part of Ser. No.626,943, filed Oct. 29, 1975, now abandoned, which in turn is acontinuation-in-part of Ser. No. 390,032, filed Aug. 20, 1973, nowabandoned.

This invention relates to chemical compounds, and more particularly to1-alkyl-1-phenyl-substituted-butenes, and to the preparation of suchcompounds, as well as to pharmaceutical compositions containing suchcompounds and the use of such compounds.

The compounds of this invention may be conveniently represented by theformula I ##STR1## wherein R is a hydrogen atom or halo having an atomicweight of from about 19 to 80, i.e., fluoro, chloro or bromo;

R¹ is lower alkyl, e.g., having from 1 to 3 carbon atoms, such asmethyl, ethyl, n-propyl and isopropyl;

Y is halo having an atomic weight of from about 80 to 127, i.e., bromoor iodo, isobutyl, tert.-butyl, cyclohexyl, cyclohexenyl, e.g.cyclohex-1-enyl, or ##STR2## wherein X is a hydrogen atom, or halohaving an atomic weight of from about 19 to 80, i.e., fluoro, chloro orbromo, or lower alkoxy, e.g., having from 1 to 4 carbon atoms, such asmethoxy, ethoxy, propoxy, or butoxy, including isomeric forms where suchexist; or a radical of the formula ##STR3## wherein each of R², R³ andR⁴, independently, is alkyl having from 1 to 3 carbon atoms, preferablyunbranched, or R² and R³ are joined to form the radical --CH₂)_(n)wherein n is an integer of 4 or 5, i.e. R² +R³ + the nitrogen atom forma pyrrolidino or piperidino ring; or R⁴ can be H; and

A is either of the structures: ##STR4## i.e., an acetyl function; or##STR5## where Z is halo having an atomic weight of from about 35 to 80,i.e., chloro or bromo; or

a pharmaceutically acceptable acid addition salt, thereof.

Thus, Compounds I comprise two subclasses, depending upon the nature ofA; R¹, Y, R and Z being as defined above: ##STR6##

Compounds Ia may be obtained by aqueous acidic treatment (process a) ofan appropriate butadienol of the formula II: ##STR7## wherein R, Y andR¹ are as defined above.

Process (a) involves aqueous acidic treatment of a compound II to obtainthe corresponding Compound Ia, and may be carried out employing as the"acidic" source a strong protonating agent, in a suitable medium, atmoderate temperatures, e.g., 10° to 100° C., preferably at 15° to 35° C.Where the protonating agent is liquid under the process conditions, itmay be used in excess to serve as the medium, however, it is preferableto include a water-miscible solvent such as ethanol or methanol.

Suitable protonating agents include mineral acids, such as hydrochloricor hydrobromic, or sulfuric acid, and aromatic- or (lower) aliphaticsulfonic acids, such as p-toluenesulfonic acid. Process (a) may likewisebe carried out using lower carboxylic acids, e.g. having from 1 to 3carbon atoms, such as acetic acid, but more vigorous reaction conditionsmay then be necessary.

If hydrochloric or hydrobromic acid is employed as the acidic source inprocess (a), then in addition to the corresponding Compound Ia product,a corresponding Compound Ib (wherein Z is accordingly either chloro orbromo) will be obtained as a co-product. Thus, by selection of reagents,either Compounds Ia or both classes of Compounds I may be obtained invarious proportions. Process (a) may be conveniently represented byReaction Scheme A, wherein R, R¹, Z and Y are as defined above: ##STR8##

Compounds II, the starting materials of Process (a) are either knowncompounds or analogs of known compounds are are obtainable by adaptionof the methods described in the literature for the preparation of suchcompounds, e.g., Belgian Pat. No. 792,079.

Compounds Ia may alternatively be prepared by process (b), reacting acompound of formula III: ##STR9## in which Y, R and R¹ are as definedand X is chloro or bromo, with a methyl-contributing organometallicreagent IV:

    CH.sub.3 --M,                                              IV

in which M is an equivalent of an active metal cation or magnesiumbromide or iodide, in an apropotic medium which is not detrimental tothe reaction and under anhydrous conditions, and hydrolyzing theresultant adduct.

Process (b) may conveniently be carried out in the conventional mannerfor carrying out a Grignard-type reaction. The M moiety of the compoundIV used may be an alkali metal, e.g. Li, however, the preferredorganometallic reagents include Grignard reagents, such as methylmagnesium halides, particularly methyl magnesium bromide. Suitableaprotic media include ethers, such as tetrahydrofuran or diethyl ether,and the reaction is preferably carried out at reduced temperatures of,for example, -30° to 0° C. The subsequent hydrolysis may be carried outin conventional manner for hydrolyzing a Grignard-type adduct, forexample, with an aqueous salt solution such as saturated ammoniumchloride solution. When, in a compound of formula III, Y is anunsubstituted piperazino radical, an additional equivalent of theorganometallic reagent is preferably used.

Compounds of formula I may be isolated and purified using conventionaltechniques. Where required, free base forms of the compounds of formulaI in which Y is a radical of formulas a¹, a², a³, or a⁴, may beconverted into acid addition salt forms in conventional manner, and viceversa. Suitable acids for salt formation include mineral acids, such ashydrochloric, hydrobromic, sulphuric and phosphoric acid, and organicacids, such as benzoic, acetic, maleic, p-toluenesulphonic andbenzenesulphonic acid.

The compounds of formula I exist as geometric isomers and may beproduced in the form of pure cis- or trans- isomers or in the form ofisomeric mixtures which may, if desired, be separated, in conventionalmanner, into individual isomers. The process (a) described above yieldsthe compounds predominantly or substantially in trans-isomeric form butother isomeric forms or mixtures may, if desired, be produced inconventional manner, for example by stereospecific synthesis or by"scrambling" the compounds obtained predominantly or substantially intrans-form as described above, e.g. by UV irradiation, and, if desired,separating the resulting isomeric mixtures using conventionaltechniques. Process (b), described above, will yield the product in thesame geometric form as the starting material. In any event, while thecompounds are preferably in pure trans-isomeric form or in the form ofisomeric mixtures in which the trans-isomer predominates, e.g. to theextent of 60 to 99%, preferably 70 to 99%, more preferably 80 to 99%, itis to be understood that the invention is not intended to be limited toany particular form of the compounds.

The compounds of formula IV are either known or may be prepared inconventional manner from available materials.

The compounds of formula III may be produced by chlorinating orbrominating a corresponding free acid of formula V: ##STR10## in whichR, R₁ and Y are as defined above, in conventional manner, for example ata temperature of from 30° to 120° C. Suitable chlorinating agentsinclude phosphorus trichloride or, preferably, thionyl chloride, andsuitable brominating agents include phosphorus tribomide. An inertsolvent, e.g. tetrahydrofuran, may suitably be employed. Alternatively,an excess of the chlorinating or brominating agent may, where it isliquid under the reaction conditions, be used to provide a reactionmedium.

The resulting compounds of formula III may be isolated and purifiedusing conventional techniques.

The compounds of formula V may be produced by saponifying a compound offormula VI: ##STR11## in which R, Y and R₁ are as defined above, and R₂is straight chain alkyl of 1 to 6 carbon atoms, preferably ethyl.

The process is suitably effected by heating the compound of formula VI,preferably at a temperature of from 70° to 120° C., in an aqueoussolution of an alkali metal hydroxide, e.g. sodium hydroxide orpotassium hydroxide. Preferably, the process is effected in the presenceof a water-miscible co-solvent, such as an alkanol of 1 to 4 carbonatoms, e.g. ethanol or methanol.

The resulting compounds of formula V may be isolated and purified usingconventional techniques.

The compounds of formula VI are either known or may be produced inconventional manner from available materials.

As indicated above, the compounds of formula I exist in the form ofgeometric isomers and the geometric form produced by process (b) dependson the configuration of the starting materials of formula III. Thus, forexample, the compounds of formula I may be obtained substantially orpredominately in trans form by process (b) by using compounds of formulaIII which are substantially or predominately in trans form. Thecompounds of formula III may be obtained substantially or predominatelyin trans form by using, initially, compounds of formula VI which aresubstantially or predominately in trans form. The compounds of formulaVI, substantially or predominately in trans form, may be produceddirectly by dehydrating a compound of formula VII: ##STR12## in which R,R₁, R₂ and Y are as defined above.

The process may be carried out by heating a compound of formula VII,suitably at a temperature of from 80° to 200° C., under vacuum, forexample 0.01 to 0.5 mm of mercury.

The resulting products may be isolated and purified using conventionaltechniques.

Other isomeric forms of the compounds of formula VI, which would lead tothe corresponding configuration in the final products of formula I, maybe produced by conventional methods, for example by stereospecificsynthesis from available materials, or by "scrambling" the compoundsobtained predominately or substantially in trans form as describedabove, e.g. by UV irradiation, and, if desired, separating the resultingisomeric mixtures using conventional techniques.

It will be appreciated that particular forms of the compounds of formulaI, produced as described above, may themselves be "scrambled" and theresulting isomeric mixtures, if desired, separated by conventionaltechniques.

The compounds of formula VII are either known or may be produced inconventional manner from available materials. A preferred method fortheir production involves reaction of a compound of formula VIII:##STR13## in which R, R₁ and Y are as defined above, with a compound offormula IX: ##STR14## in which R₂ is as defined above, in an aproticsolvent and under anhydrous conditions, and hydrolysing the resultingadduct.

Suitable solvents include ethers, such as tetrahydrofuran. Suitablereaction temperatures are moderate, for example from 15° to 30° C.

The subsequent hydrolysis may suitably be carried out using water, anaqueous acid base, or an aqueous solution of a salt, e.g., concentratedammonium hydroxide or dilute sulphuric acid.

The compounds of formula IX may be produced, conveniently in situ, byheating activated zinc, preferably finely divided, e.g., 20 mesh, withR² -bromoacetate in an aprotic solvent, e.g., tetrahydrofuran. Theprocess is, preferably, carried out in the presence of trimethyl borate.The treatment is suitably effected at a temperature of from 15° to 30°C. When trimethyl borate is used in the in situ preparation of acompound IX, it is convenient to include in the hydrolysis step, whenusing an aqueous base, in addition, glycerine.

The resulting compounds of formula VII may be isolated and purifiedusing conventional techniques.

Compounds VII and IX are either known or may be prepared in conventionalmanner from available materials, and many are commercially available.

Process (b) and associated processes are conveniently represented byReaction Scheme, B, below, in which R, R¹, R², X, Y and M are as definedabove: ##STR15##

STATEMENT OF UTILITY

The compounds of formula I are useful because they possesspharmacological activity in animals. In particular, the compounds I areuseful as anti-inflammatory agents as indicated by the Carrageenaninduced edema test on rats (oral administration at 5 to 200 mg./kg.).For such use, the compounds may be combined with a pharmaceuticallyacceptable carrier, and such other conventional adjuvants as may benecessary, and administered orally in such forms as tablets, capsules,elixirs, suspensions and the like or parenterally in the form of aninjectable solution or suspension. The dosage administered will, ofcourse, vary depending upon the compounds used and the mode ofadministration. However, in general, satisfactory results are obtainedwhen administered at a daily dosage of from about 1 milligram to about200 milligrams per kilogram of body weight, preferably given in divideddoses 2 to 4 times a day, or in sustained release form. For most mammalsthe administration of from about 70 milligrams to about 1500 milligramsof the compound per day provides satisfactory results and dosage formssuitable for internal administration comprise from about 20 milligramsto about 800 milligrams of the compound in admixture with a solid orliquid pharmaceutical carrier or diluent, e.g., a sterile suspension ora solid composition, comprising, for example, from about 5 to 95% of acompound I, e.g., from about 5% to 50% of a compound I.

As noted above, oral administration with carriers may take place in suchconventional forms as tablets, dispersible powders, granules, capsules,syrups and elixirs. Such compositions may be prepared according to anymethod known in the art for manufacture of pharmaceutical compositions,and such compositions may contain one or more conventional adjuvants,such as sweetening agents, flavoring agents, coloring agents andpreserving agents, in order to provide an elegant and palatablepreparation. Tablets may contain the active ingredient in admixture withconventional pharmaceutical excipients, e.g., inert diluents such ascalcium carbonate, sodium carbonate, lactose and talc, granulating anddisintegrating agents, e.g., starch and alginic acid, binding agents,e.g., starch, gelatin and acacia, and lubricating agents, e.g.,magnesium stearate, stearic acid and talc. The tablets may be uncoatedor coated by known techniques to delay disintegration and absorption inthe gastro-intestinal tract and thereby provide a sustained action overa longer period. Similarly, suspensions containing, for example, fromabout 0.5 to 5% of suspending agent, syrups containing, for example, 10to 50% of sugar, and elixirs containing, for example from about 20 to50% of ethenol may contain the active ingredient in admixture with anyof the conventional excipients utilized for the preparation of suchcompositions, e.g., suspending agents (methylcellulose, tragacanth andsodium alginate), wetting agents (lecithin, polyoxyethylene stearate andpolyoxyethylene sorbitan monooleate) and preservatives(ethyl-p-hydroxybenzoate). Capsules preferably contain an activeingredient admixed with an inert diluent, e.g., a solid diluent such ascalcium carbonate, calcium phosphate and kaolin or a liquid diluent,such as polyethylene glycol or an edible oil, e.g., peanut, corn orsesame oil. The preferred pharmaceutical compositions from thestandpoint of preparation and ease of administration are orallyadministrable compositions, particularly tablets and solid or liquiddiluent-filled capsules.

When the substituent Y is a radical of structures a¹, a², a³ or a⁴ thensuch compounds I may be similarly administered in the form of theirnontoxic pharmaceutically acceptable acid addition salts. Such salts donot materially differ from the free base in their pharmacologicaleffects and are included within the scope of the invention. The acidaddition salts are readily prepared by reacting the base withpharmacologically acceptable acids in conventional manner.Representative of such salts are the mineral acid salts such as thehydrochloride, hydrobromide, sulfate, phosphate and the like and theorganic acid salts such as the benzoate, acetate, maleate,p-toluenesulfonate, benzenesulfonate and the like.

Representative formulations of a tablet and a capsule prepared byconventional techniques are as follows:

    ______________________________________                                                          Weight                                                      Ingredient          Tablet    Capsule                                         ______________________________________                                        2-(p-biphenylyl)-2-penten-4-one                                                                   50        50                                              (about 99% trans)                                                             Tragacanth          10                                                        Lactose             197.5     250                                             Corn Starch         25                                                        Talcum              15                                                        Magnesium Stearate  2.5                                                       ______________________________________                                    

In the following examples, which illustrate the invention, temperaturesare in degrees centigrate, and room temperature is 20° to 30° C., unlessindicated otherwise. Olefinic products are understood to be insubstantially trans form, unless indicated otherwise. Trans forms areunderstood to be those in which the olefinic hydrogen atom and R¹ are onopposite sides of the double bond.

EXAMPLE 1 2-(p-Biphenylyl)-2-penten-4-one* ##STR16##2-(p-biphenylyl)-4-chloro-2,4-pentadiene** ##STR17##

To a solution of 1.5 g. of 2-(p-biphenylyl)-3,4-pentadien-2-ol in 50 ml.of methanol, there is slowly added 2.5 ml. of concentrated hydrochloricacid (12 N). After 3 hours at room temperature, a 10% aqueous solutionof sodium acetate is added to the reaction mixture. The precipitatewhich is formed is filtered and washed with water, and dried overphosphorus pentoxide giving a light yellow solid. The filtrate is thenconcentrated and more solid is obtained and washed and dried in the samemanner. The combined solids are then purified via silica gel preparativeplates eluting with methylene chloride. There is obtained two fractions;a first fraction of 2-(p-biphenylyl)-2-penten-4-one, m.p. 130°-133° C.,and a second fraction of 2-(p-biphenylyl)-4-chloro-2,4-pentadiene, m.p.75°-79° C.

EXAMPLE 2 2-(p-Biphenylyl)-2-penten-4-one and2-(p-biphenylyl)-4-chloro-2,4-pentadiene.

To a solution of 10 g. of 2-(p-biphenylyl)-3,4-pentadien-2-ol in 200 ml.of anhydrous methanol is added 3 ml. of concentrated hydrochloric acid.The resulting mixture is stirred at room temperature for 3 hours andthen in an ice bath for 2 hours. Solids form are are filtered off andrecrystallized from pentane to obtain 2-(p-biphenylyl)-2-penten-4-one.

The filtrate is evaporated to obtain an oil which is purified by placingon a silica gel preparative plate and eluting with methylene chloride toobtain 2-(p-biphenylyl)-4-chloro-2,4-pentadiene, which may also bedesignated 4-(p-biphenylyl)-2-chloro-1,3-pentadiene.

Repeating the procedure of this example, but using in place of the2-(p-biphenylyl)-3,4-pentadien-2-ol an equivalent amount of the compoundof column (A) there is similarly obtained the compounds of columns (B)and (C):

    ______________________________________                                        A            B           C                                                    ______________________________________                                        (a) 2-(p-tert.   2-(p-tert.- 4-(p-tert.butyl-                                     butylphenyl- butylphenyl-                                                                              phenyl)-2-chloro-                                    3,4-pentyldien-2-ol                                                                        2-penten-   1,3-pentadiene.                                                   4-one                                                        (b) 2-(p-bromo-  2-(p-bromo- 4-(p-bromophenyl)-                                   phenyl)-3;   phenyl)-    2-chloro-1,3-                                        4-pentadien-2-ol                                                                           2-penten-   pentadiene                                                        4-one                                                        (c) 2-(p-cyclo-  2-(p-cyclo- 4-(p-cyclohexyl-                                     hexyl-m-     hexyl-m-    m-chlorophenyl)-2-                                   chlorophenyl)-                                                                             chloro-     chloro-1,3-penta-                                    3,4-         phenyl-2-   diene                                                pentadien-2-ol                                                                             penten-4-one                                                 (d) 2-(p-isobutyl-                                                                             2-(p-isobutyl-                                                                            4-(p-isobutyl-                                       phenyl)-3,4- phenyl)-2-  phenyl)-2-chloro-                                    penta-       penten-     1,3-pentadiene                                       dien-2-ol    4-one                                                        (e) 2-(p-bi-     4-(p-bi-    4-(p-biphenylyl)-                                    phenylyl)-   phenylyl)-  2-chloro-1,3-                                        3,4-heptadien-                                                                             3-hepten-2-one                                                                            heptadiene                                           2-ol                                                                      (f) 2(p-1'-cyclo-                                                                              2(p-1'-cyclo-                                                                             4-(p-1'-cyclo-                                       hexenyl-     hexenyl-    hexenyl-phenyl)-2-                                   phenyl)-3,4- phenyl)-2-  chloro-1,3-pentadiene                                pentadien-   penten-4-one                                                     2-ol                                                                      (g) 2-(p-morpho- 2-(p-morpho-                                                                              4-(p-morpholinophenyl)-                              linophenyl)- lino-       2-chloro-1,3-pentadiene                              3,4-pentadien-                                                                             phenyl)-2-  hydrochloride                                        2-ol         penten-4-                                                                     one hydro-                                                                    chloride                                                     (h) 2-[p-(N-methyl-                                                                            2-[p-(N-methyl-                                                                           4-[p-(N-methyl-                                      piperazinyl)-                                                                              piperazinyl)-                                                                             piperazinyl)phenyl]-                                 phenyl]-     phenyl]-    2-chloro-1,3-penta-                                  3,4-pentadien-                                                                             2-penten-4-one                                                                            diene hydrochloride                                  2-ol         hydrochloride                                                (i) 2-(p-3-pyrro-                                                                              2-(p-3-pyrro-                                                                             4-(p-3-pyrrolinyl-                                   linyl-       linyl-      phenyl)-2-chloro-1,3-                                phenyl)-3,4- phenyl)-2-  pentadiene                                           penta-       penten-4-   hydrochloride                                        dien-2-ol    one hydro-                                                                    chloride                                                     ______________________________________                                    

EXAMPLE 3

Repeating the procedure of Example 1, but using in place of theconcentrated hydrochloric acid used therein, 200 mg. ofp-toluenesulphonic acid hydrate in 10 ml. of 90% aqueous ethanol and thereaction mixture kept at room temperature for 18 hours, there issimilarly obtained 2-(p-biphenylyl)-2-penten-4-one.

EXAMPLE 4 [Process (a)]

In manner analogous to Example 3, but employing appropriate startingmaterials in approximately equivalent amounts, the compounds of Examples2(a) (B), (b) (B), (c) (B), (d) (B), (e) (B) and (f) (B) and thep-toluenesulphonate forms of the compounds of Examples 2(g) (B), 2(h)(B) and 2(i) (B) may be obtained.

EXAMPLE 5 2-(p-Biphenylyl)-2-penten-4-one [process (b)] (a)3-(4-Biphenylyl)-2-butenoic acid ethyl ester

6.45 g (0.1 mole) of activated zinc metal (20 mesh) is placed in a flaskfitted with a septum inlet and a magnetic stirrer. The system ismaintained under a nitrogen atmosphere and kept at a temperature of 25°C. on a water bath. A solution of 19.6 g (0.1 mole) of 4-acetylbiphenylin 75 ml of dry tetrahydrofuran and 75 ml of trimethyl borate (distilledfrom calcium hydride) is injected and the mixture stirred. 11.1 ml (0.1mole) of freshly distilled ethyl bromoacetate is injected in one shotand the mixture stirred at 25° C. for 12 hours. A mixture of 25 ml ofconcentrated ammonium hydroxide and 75 ml of glycerine is added, and theaqueous phase is separated and extracted thrice with 25 ml portions ofdiethyl ether. The combined organic extracts are dried over anhydrousmagnesium sulphate and the diethyl ether removed on a rotary evaporator;the residue is vacuum distilled and the fraction distilling at 0.125 mmat 171°-172° C. is collected. Recrystallisation from petroleum etheryields the heading compound.

(b) 3-(4-biphenyl)-2-butenoic acid

The product resulting from (a), above, is mixed with 6 g of 85%potassium hydroxide in 100 ml of aqueous ethanol and the resultingmixture heated on a steam bath for 30 minutes. The mixture is thencooled, poured into ice and extracted thrice with 25 ml portions ofdiethyl ether. The aqueous phase is filtered over Celite and thefiltrate acidified with 2 N hydrochloric acid to pH 4 and cooled. Theresulting precipitate is filtered, washed with ether, air dried withsuction and then dried under high vacuum at 50° C. to yield the headingcompound.

(c) 3-(4-Biphenylyl)-2-butenoic acid chloride

The crude product, resulting from (b), above, is dissolved in 200 ml ofdry tetrahydrofuran and 4 ml (0.055 mole) of thionyl chloride is added.The solution is refluxed under a nitrogen atmosphere for 3 hours and thesolvent and excess thionyl chloride then distilled off. The resultingresidue is flash distilled in a microdistillation apparatus at 145°-153°C. and 0.075 mm to yield the heading compound.

(d) 2-(p-Biphenylyl)-2-penten-4-one

10.0 g (0.039 mole) of the crude acid chloride from (c), above, isdissolved in 200 ml of dry tetrahydrofuran and the solution placed in a500 ml round bottom flask fitted with a septum inlet and magneticstirrer, and held under a nitrogen atmosphere. The solution is cooled to-30° C. in a dry ice/isopropanol bath and 19.5 ml (0.039 mole) of acommercial 2 M methyl magnesium bromide solution in dry toluene isadded, dropwise, over 30 minutes. After the addition is complete, themixture is allowed to warm to room temperature and then stirred for 1hour. The reaction is quenched by the addition of 20 ml of saturatedammonium chloride solution and the organic layer is separated. Theaqueous layer is extracted twice with 20 ml portions of ether and thecombined organic extracts are then dried over anhydrous magnesiumsulphate and evaporated to yield the heading compound, m.p. 130° to 133°C., after recrystallisation from petroleum ether.

EXAMPLE 6

Repeating the procedure of Examples 1 through 3, but using in place ofthe 2-(p-biphenylyl)-3,4-pentadien-2-ol, an approximately equivalentamount of 3-(p-biphenylyl-4,5-hexadiene-3-ol, there is similarlyobtained 3-(p-biphenylyl)-3-hexene-5-one, mp 63°.

EXAMPLE 7

In manner analogous to Example 5 but employing appropriate startingmaterials in approximately equivalent amounts, the compounds of Examples2(a) (B), (b) (B), (c) (B), (d) (B), (e) (B), (f) (B), (g) (B), (h) (B),(i) (B); and of Example 6 may be obtained.

What is claimed is:
 1. A compound of the formula ##STR18## wherein R isa hydrogen atom or halo having an atomic weight of from about 19 to80;R¹ is alkyl having from 1 to 3 carbon atoms; and X is a hydrogenatom, halo having an atomic weight of from about 19 to 80, or alkoxyhaving from 1 to 4 carbon atoms.
 2. A compound of claim 1 wherein R¹ ismethyl.
 3. A compound of claim 1 wherein R is a hydrogen atom.
 4. Acompound of claim 3 wherein X is a hydrogen atom, and R¹ is methyl.
 5. Apharmaceutical composition suitable for use as an anti-inflammatorycomprising an amount of a compound of claim 1 effective in reducinginflammation and a pharmaceutically acceptable carrier for saidcompound.
 6. A method of treating inflammation in an animal in need ofsuch treatment, comprising internally administering to said animal anamount of a compound of claim 1, effective in reducing saidinflammation.
 7. A compound of claim 1, in trans form.
 8. The compoundof claim 1 which is 2-p(biphenylyl)-2-penten-4-one(trans).
 9. Acomposition of claim 5 in which the compound is present in an amount offrom about 20 milligrams to about 800 milligrams.
 10. A composition ofclaim 5 in which the carrier is a solid.
 11. A composition of claim 5 inwhich the compound is 2-(p-biphenylyl)-2-penten-4-one (trans).
 12. Amethod of claim 6 in which from about 70 milligrams to about 1500milligrams of the compound are administered to a mammal daily.
 13. Amethod of claim 6 in which the compound is2-(p-biphenylyl)-2-penten-4-one (trans).